Repertoire and immunofocusing of CD8 T cell responses generated by HIV-1 gag-pol and expression library immunization vaccines

R. A K Singh, Michael A Barry

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Several gene-based vaccine approaches are being tested to drive multivalent cellular immune responses to control HIV-1 viral variants. To compare the utility of these approaches, HLA-A*0201 transgenic mice were genetically immunized with plasmids encoding wild-type (wt) gag-pol, codon-optimized (CO) gag-pol, and an expression library immunization (ELI) vaccine genetically re-engineered to express non-CO fragments of gag and pol fused to ubiquitin for proteasome targeting. Equimolar delivery of each vaccine into HLA-A*0201 transgenic mice generated CD8 T cell responses, with the ELI vaccine producing up to 10-fold higher responses than the wt or CO gag-pol plasmids against cognate and mutant epitopes. All three vaccines generated multivalent CD8 responses against varying numbers of epitopes after priming. However, when the animals were immunized again, the wt and CO gag-pol vaccines boosted only the responses against a subset of epitopes and attenuated the responses against all other Ags including epitopes from clade and drag-resistant viral variants. In contrast, the ELI vaccine boosted CD8 responses against all of the gag-pol Ags and against mutant epitopes from clade and drug-resistant variants. These data suggest that HIV-1 vaccines expressing structurally intact gag and pol proteins drive immunofocused CD8 responses that reduce the repertoire of T cell responses. In contrast, the genetically re-engineered ELI vaccine appears to better maintain the multivalent CD8 responses that may be required to control HIV-1 viral variants.

Original languageEnglish (US)
Pages (from-to)4387-4393
Number of pages7
JournalJournal of Immunology
Volume173
Issue number7
StatePublished - Oct 1 2004
Externally publishedYes

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HIV-1
Immunization
Vaccines
T-Lymphocytes
Epitopes
Codon
Transgenic Mice
gag-pol Fusion Proteins
Plasmids
AIDS Vaccines
Proteasome Endopeptidase Complex
Ubiquitin
Cellular Immunity
Pharmaceutical Preparations
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Repertoire and immunofocusing of CD8 T cell responses generated by HIV-1 gag-pol and expression library immunization vaccines. / Singh, R. A K; Barry, Michael A.

In: Journal of Immunology, Vol. 173, No. 7, 01.10.2004, p. 4387-4393.

Research output: Contribution to journalArticle

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